Hussain, Nasir

Background Knee osteoarthritis (OA) is a leading cause of chronic pain and disability, with limited disease modifying therapies. While glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have established cardiometabolic benefits and have been associated with reductions in knee OA related pain, it is unclear whether they can reduce progression to total knee arthroplasty (TKA). Methods We conducted a retrospective cohort study using the TriNetX Global Research Network, identifying adults with knee OA diagnosed between January 1, 2010, and December 31, 2024. Patients were stratified by GLP-1 RA exposure class (any GLP-1 RA or new generation agents, semaglutide or tirzepatide) and treatment duration (1 or 3 years), and then compared with propensity score matched non-exposed cohorts balanced for age, sex, race, musculoskeletal diagnoses, obesity related conditions, body mass index, and proxies for healthcare access. The primary outcome was cumulative incidence of TKA at 1, 3, 5, and 8 years. Hazard ratios (HRs) were estimated by Cox proportional hazards models and absolute risk differences from Kaplan–Meier curves, expressed as exposed minus non-exposed. Results After propensity score matching, cohort sizes ranged from 13 351 (new generation GLP-1 RA, 3 year exposure) to 42 062 patients (any GLP-1 RA, 1 year exposure). GLP-1 RA use was associated with significantly lower cumulative TKA incidence across all exposure classes, durations, and follow-up intervals (all p<0.001). With 1 year exposure to any GLP-1 RA, the absolute risk difference at 8 years was −2.80 percentage points (HR 0.90, 95% CI 0.83 to 0.98). Risk reductions were greater with new generation agents and longer duration: 3 year exposure to semaglutide or tirzepatide gave an absolute risk difference of −4.71 percentage points at 8 years (HR 0.72, 95% CI 0.67 to 0.78). Conclusions In this large, multicenter, real world cohort study, GLP-1 RA use was associated with a significantly reduced long term risk of TKA in patients with knee OA, with effects that were greater with longer treatment duration and newer generation agents. These duration and agent dependent associations are consistent with potential disease modifying activity beyond weight loss alone, although prospective trials are needed to establish causality and define optimal treatment targets.

Estimates of fibromyalgia prevalence vary widely worldwide due to differences in diagnostic criteria, study methodology, and population characteristics. Accurate estimates are essential to inform population-level surveillance, guide resource allocation, and highlight disparities in disease recognition and access to care. The objective of this systematic review and meta-analysis was to determine the global prevalence of fibromyalgia in the general population, and secondarily to identify factors moderating prevalence variation and to assess prevalence in defined at-risk subpopulations. Pooled prevalence estimates with 95% confidence intervals (CIs) were calculated using the inverse variance heterogeneity model with Freeman–Tukey transformation. Subgroup analyses were performed by sex, diagnostic criteria, country, and other study characteristics, and meta-regression assessed moderators including publication year and Human Development Index (HDI). Of 21,645 records identified, 1,728 underwent full-text review and 882 studies were included in the final analysis. Across 38 countries and 30,070,032 individuals (188 studies), the pooled fibromyalgia prevalence in the general population was 1.40% (95% CI, 0.49–2.47), with substantial heterogeneity (I 2 = 100%) and very low certainty of evidence. Among at-risk subpopulations (9,771,123 participants; 768 studies), prevalence was markedly higher in autoimmune and inflammatory conditions, such as chronic urticaria (37.1%), interstitial cystitis (30.8%), systemic sclerosis (20.6%), celiac disease (20.5%), and inflammatory bowel disease (19.9%), and elevated in chronic pain, rheumatologic, and post-infection cohorts. Meta-regression identified publication year (β = 0.008, P < .001) and HDI (β = 0.725, P = .002) as significant moderators of prevalence. In conclusion, fibromyalgia affects 1% to 2% of the global population, with substantially higher rates in at-risk subpopulations. Temporal and socioeconomic trends emphasize diagnostic inconsistency and global disparities in care.

Importance Chronic pain is a leading cause of disability, and many affected patients rely on long-term opioid therapy despite its unfavorable adverse effect profile. Spinal cord stimulation is an established therapy for chronic pain that may secondarily reduce opioid consumption by providing sustained analgesia. Objective To quantify changes in opioid use following spinal cord stimulation implantation for the treatment of chronic pain through a systematic review and meta-analysis. Data sources We conducted a comprehensive search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus from each database’s inception to July 1, 2024. Study selection We included studies describing patients who underwent spinal cord stimulator implantation for the treatment of chronic pain. A total of 2,784 potential studies were identified and screened by multiple independent reviewers, yielding a final total of 43 studies included in the systematic review. Data extraction and synthesis Data extraction was completed by multiple independent reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Meta-analysis Of Observational Studies in Epidemiology guidelines. A random effects model with Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate pooled estimates. Certainty assessment was performed following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Main outcome(s) and measure(s) The primary outcomes were change in continuous opioid use (ie, morphine milligram equivalent (MME)) and categorical opioid use (yes/no) from preimplantation to 12 months following spinal cord stimulator implantation. Results Meta-analysis of 12 month continuous MME use comprising 22 study comparisons (1,666 individuals) revealed a weighted mean difference of −18.06 MME (95% CI −24.41 to −11.70; 95% prediction interval −38.29 to 2.17; p<0.001). Meta-analysis of categorical opioid use at 12 months comprising 24 study comparisons (1,527 individuals) revealed an OR of 0.47 (95% CI 0.30 to 0.75; 95% prediction interval 0.10 to 2.11; p=0.003), signifying lower odds of opioid continuation. Conclusions and relevance Spinal cord stimulation is associated with reduced opioid dose consumption and increased odds of opioid cessation at 12 months postimplantation compared with baseline in patients with chronic pain; however, both of these conclusions are supported by evidence of very low GRADE certainty. PROSPERO registration number CRD42024574921.

BACKGROUND: Recent years have seen considerable growth and significant changes in the anesthesiology residency application process. Although the National Residency Match Program provides data on attributes of successfully matching applicants, it does not provide detailed characteristics of applicants’ research portfolio. This single-program retrospective analysis aims to characterize granular aspects of applicant research experiences to determine whether research involvement is linked to higher odds of matching. METHODS: Applications from interviewed United States allopathic (US-MD) and osteopathic (US-DO) applicants at a single anesthesiology residency program were analyzed for research experience. The primary outcome assessed was the association of any research experience with odds of ranked-to-match and the association of specific types of research experience with ranked-to-match. Secondary outcomes included the association of medical degree type (US-MD vs US-DO) or affiliation of medical school with an anesthesiology residency program to the number of research experiences, and the association of research experiences with the United States Medical Licensing Examination (USMLE) Step 1 score type (Pass/Fail vs Scored). RESULTS: Applicants with at least one research experience were more likely to be ranked-to-match than applicants without research experience (odds ratio [OR]: 2.16, 95% confidence interval [CI], [1.55–3.02], P < .001). Similar odds were demonstrated for applicants with at least one peer-reviewed publication compared to no peer-reviewed publications (OR: 2.25, 95% CI, [1.79–2.82], P < .001), and at least one anesthesiology-related research experience compared to no anesthesiology-related research experience (OR: 1.76, 95% CI, [1.36–2.26], P < .001. Applicants from US-MD schools were more likely to have research experience than those from US-DO schools ( P < .001); applicants from a medical school affiliated with an anesthesiology residency were more likely to have research experience than applicants from unaffiliated medical schools ( P < .001); and applicants with Pass/Fail USMLE Step 1 examinations were more likely than their Scored counterparts to report at least one research experience ( P < .001). CONCLUSIONS: Applicant research is associated with greater odds of being ranked-to-match in anesthesiology residency. Applicants from US-MD schools and schools affiliated with anesthesiology residency programs have significantly greater rates of reporting at least one research experience. There is a trend toward a higher incidence of reporting at least one research experience with the change of USMLE Step 1 policy toward a Pass/Fail examination.

Background: The use of spinal cord stimulation (SCS) for managing severe refractory chronic pain has expanded considerably due to positive statistical evidence regarding its use; however, the statistical robustness of the underlying randomized controlled trials (RCTs) requires further scrutiny. One such tool that can be used for this purpose is the fragility index, which quantifies how many individual outcome events must be altered for an outcome to lose statistical significance. Thus the index can be used quantitatively to assess the stability and robustness of an RCT’s conclusions, with higher values indicating increased trial stability. This study assesses the fragility of pain outcomes across RCTs investigating SCS for chronic pain to better understand the quality and robustness of evidence. Methods: A systematic search was conducted for RCTs assessing SCS for any chronic pain indication. The primary outcome was an evaluation of the trial-specific fragility index for the prespecified pain primary outcomes of RCTs. Secondary outcomes included an evaluation of fragility for (1) specified indications for SCS therapy, (2) reported pain outcomes appearing in three or more RCTs, (3) the presence/absence of a conflict of interest, and (4) comparisons of SCS to conservative management or different SCS waveform modalities. Results: A total of 30 RCTs were included. The median (interquartile range [IQR]) fragility index across the primary outcome of all trials was 5.45 (3.00 to 11.45). There was no statistical difference between the (1) types of outcomes (dichotomous vs. continuous; P = 0.710), (2) primary versus secondary pain outcomes ( P = 0.771), or (3) presence versus absence of trial conflict of interest ( P = 0.753). Indications with a median (IQR) fragility score greater than three included persistent spinal pain syndrome type 2 with a score of 8.00 (2.80 to 12.60), painful diabetic neuropathy with a score of 6.00 (3.00 to 11.80), complex regional pain syndrome with a score of 7.20 (4.62 to 81.50), mixed etiologies with a score of 9.00 (3.00 to 38.00), and other etiologies with a score of 3.00 (1.00 to 8.55). Conclusions: This study suggests that the majority of RCTs investigating primary pain outcomes after SCS therapy are robust with relatively high fragility scores. Reporting the fragility of outcomes in trials can provide a more comprehensive assessment of trial robustness and can further aid clinicians in interpreting trial results and making informed treatment decisions.

Background Peripheral nerve stimulation (PNS) has emerged as a promising neurostimulation modality, yet its effectiveness and durability for chronic pain remain uncertain. We conducted a systematic review and meta-analysis to evaluate changes in pain intensity following implantable PNS therapy. Methods Eligible studies included adults (≥18 years) with chronic pain treated with an implantable PNS system, and pain intensity was assessed at baseline and follow-up time points. The primary outcome was change in pain intensity from baseline to 6 months after PNS implantation. Secondary outcomes included changes in pain intensity at 3, 12 and 24 months after PNS implantation. Standardized mean differences (Hedges’ g ) were pooled using a random-effects model. Results A total of 106 studies comprising 9272 patients were included. PNS was associated with large, statistically significant reductions in pain intensity from baseline to all time points: 3 months (Hedges’ g 2.92; 95% CI 2.62 to 3.21), 6 months (Hedges’ g 3.08; 95% CI 2.68 to 3.48), 12 months (Hedges’ g 2.68; 95% CI 2.30 to 3.05) and 24 months (Hedges’ g 2.08; 95% CI 1.68 to 2.48) (all p<0.001). However, the certainty of evidence as assessed by the Grading of Recommendations Assessment, Development and Evaluation criteria was rated as low for the primary outcome, due to pooling from observational studies, risk of bias, and heterogeneity (statistical, clinical and methodological). Subgroup analyses revealed no differences by study design or device type, while smaller effect sizes were reported in industry-funded studies and those with declared conflicts of interest. The largest effect sizes were observed in pelvic and upper extremity pain, whereas the smallest in truncal pain. Conclusion Implantable PNS provides persistent and clinically meaningful analgesia for chronic pain, with benefits sustained up to 24 months. These findings support broader clinical adoption and provide evidence to inform pay0r coverage and policy decisions.

Background Peripheral nerve stimulation (PNS) is an emerging neuromodulation therapy for chronic pain, yet its use in clinical practice varies significantly. Although temporary PNS is widely incorporated, either as a screening trial or a treatment itself, the evidence supporting the use of temporary PNS prior to permanent implantation is limited. We aimed to compare pain relief, opioid consumption, and adverse events between an approach implementing temporary PNS before permanent implantation (temporary-to-permanent (TTP)) vs proceeding directly to permanent PNS implantation (direct-to-permanent (DTP)). Methods A multicenter retrospective study was undertaken at seven major academic institutions from January 1, 2014, to January 1, 2024. Adult patients who underwent permanent PNS implantation for the treatment of chronic pain conditions were included and were divided into TTP or DTP cohorts based on their clinical approach. The dual primary outcomes were pain relief and opioid consumption (in oral morphine equivalents) at 6 months compared with baseline before any PNS therapy. Multivariable Tobit regression analysis was performed to identify predictors of pain relief at 6 months using a stepwise approach. Results A total of 130 patients were analyzed (54 in TTP approach, 76 in DTP approach). Patient-reported percentage pain relief was 56.7%±27.9% at 6 months compared with baseline (before PNS implantation) in the TTP cohort, and 45.1%±33.6% in the DTP cohort. The estimated mean percentage pain relief at 6 months was similar in the TTP and DTP cohorts (between-group difference 15.24%; 95% CI −0.32 to 30.80, p=0.052), with consistent findings after sensitivity analysis with multiple imputation. Opioid consumption declined similarly in the TTP (−3.1±9.9 mg) and DTP (−2.1±8.1 mg) cohorts at 6 months with no statistical difference between cohorts (mean between-group difference: −1.00, 95% CI −4.57 to 2.57, p=0.580), and with consistent findings after sensitivity analysis. Device explantation rates and adverse event profiles were comparable between cohorts. Conclusion Although temporary PNS is widely performed prior to permanent PNS implantation, there was no evidence that the TTP approach is associated with superior analgesic outcomes compared with the DTP approach. Further, patients in both approaches achieved clinically meaningful pain relief at 6 months compared with baseline status prior to PNS therapy.